期刊
CANCER GENE THERAPY
卷 18, 期 4, 页码 229-239出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2010.68
关键词
MSC; TRAIL; resistance; colorectal carcinoma
类别
资金
- Federal State of Saxonia-Anhalt [FKZ: 3646A/0907]
- German Ministry of Education and Research
Tumor-integrating multipotent mesenchymal stromal cells (MSC) expressing transgenes with anti-tumor activity may serve as vehicles for tumor therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents such a factor; however, TRAIL-resistant tumor cells exist. Based on our previous work, here we investigated whether MSC with lentiviral TRAIL expression (TRAIL-MSC) inhibit the growth of TRAIL-resistant colorectal carcinoma (CRC) cells. Our data show that TRAIL-MSC induce apoptosis in selected TRAIL-resistant CRC cell lines and effectively inhibit the growth of TRAIL-resistant HCT8 cells. This sensitization to TRAIL-induced apoptosis required the presence of MSC-expressed TRAIL. However, for the first time we show that selected CRC cells are resistant to TRAIL-MSC. In the cell line HT29, this resistance could be overcome by concomitant subapoptotic genotoxic damage in vitro. However, such sensitization was not achieved in vivo as treatment of mixed HT29/TRAIL-MSC xenografts with 5-FU rather resulted in enhanced growth. Taken together, our data prove that TRAIL-MSC overcome TRAIL resistance in selected CRC cells through direct intercellular interaction and may, therefore, represent a clinical tool to overcome TRAIL resistance. However, such potential clinical use requires further preclinical studies as our data also prove that TRAIL-MSC-resistant CRC cells exist. Our data add to the notion that TRAIL resistance of CRC cells is conferred by different mechanisms. Cancer Gene Therapy (2011) 18, 229-239; doi: 10.1038/cgt.2010.68; published online 29 October 2010
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